دورية أكاديمية
AP1S3 mutations are associated with pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking
| العنوان: | AP1S3 mutations are associated with pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking |
|---|---|
| المؤلفون: | Setta-Kaffetzi, Niovi, Simpson, Michael A., Navarini, Alexander A., Patel, Varsha M., Lu, Hui-Chun, Allen, Michael H., Duckworth, Michael, Bachelez, Hervé, Burden, A. David, Choon, Siew-Eng, Griffiths, Christopher E.M., Kirby, Brian, Kolios, Antonios, Seyger, Marieke M.B., Prins, Christa, Smahi, Asma, Trembath, Richard C., Fraternali, Franca, Smith, Catherine H., Barker, Jonathan N., Capon, Francesca |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2014 |
| المجموعة: | University of Glasgow: Enlighten - Publications |
| الوصف: | Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | Setta-Kaffetzi, N. et al. (2014) AP1S3 mutations are associated with pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking. American Journal of Human Genetics , 94(5), pp. 790-797. (doi:10.1016/j.ajhg.2014.04.005 ) |
| الإتاحة: | https://doi.org/10.1016/j.ajhg.2014.04.005Test http://eprints.gla.ac.uk/104674Test/ |
| رقم الانضمام: | edsbas.C7A3F144 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |